tbuckley/cabot-search huggingface dataset:
Human IgE mAbs identify major antigens of parasitic worm infection
Authors: Azadeh Hadadianpour, Jacob Daniel, Jian Zhang, Benjamin W. Spiller, Asta Makaraviciute, Åsa M. DeWitt, Heather S. Walden, Robert G. Hamilton, R. Stokes Peebles, Thomas B. Nutman, Scott A. Smith
Journal: Journal of Allergy and Clinical Immunology (2022)

Much of our understanding of the targets of IgE comes from studies of allergy, though little is known about the natural immunogenic targets seen after parasitic worm infections.We used human monoclonal antibodies (mAbs) for an unbiased and comprehensive characterization of the immunodominant antigens targeted by IgE in conditions like allergy or helminth infection that are associated with elevated levels of IgE.Using human hybridoma technology to immortalize IgE encoding B-cells from peripheral blood of subjects with filarial infections and elevated IgE, we generated naturally occurring human IgE mAbs. B-cell cultures were screened in an unbiased manner for IgE production without regard to specificity. Isolated IgE mAbs were then tested for binding to Brugia malayi somatic extracts using ImmunoCAP, immunoblot, and ELISA. Immunoprecipitation followed by mass spectrometry proteomics was used to identify helminth antigens that were then expressed in Escherichia coli for IgE binding characterization.We isolated 56 discrete IgE mAbs from 7 individuals with filarial infections. From these mAbs, we were able to definitively identify 19 filarial antigens. All IgE mAbs targeted filarial excreted/secretory proteins, including a family of previously uncharacterized proteins. Interestingly, the transthyretin-related antigens acted as the dominant inducer of the filaria-specific IgE antibody response. These filaria-specific IgE mAbs were potent inducers of anaphylaxis when passively administered to human FcεRI-expressing mice.We generated human hybridomas secreting naturally occurring helminth-specific IgE mAbs from filarial-infected subjects. This work provides much-needed insight into the ontogeny of helminth-induced immune response and IgE antibody response.
Anchoring endoscopic mucosal resection versus conventional endoscopic mucosal resection for large nonpedunculated colorectal polyps: a randomized controlled trial
Authors: Chang Kyo Oh, Young-Seok Cho, Sung Hak Lee, Bo-In Lee
Journal: Endoscopy (2022)

Abstract Background Colorectal polyps &gt; 10 mm in size are often incompletely resected. Anchoring-endoscopic mucosal resection (A-EMR) is the technique of making a small incision at the oral side of the polyp using a snare tip after submucosal injection to avoid slippage during ensnaring. This study was performed to evaluate whether A-EMR could increase the complete resection rate for large colorectal polyps compared with conventional endoscopic mucosal resection (C-EMR). Methods Polyps with sizes of 10–25 mm were randomly allocated to either the A-EMR or the C-EMR groups. Results 105 and 106 polyps were resected using A-EMR and C-EMR, respectively. In the intention-to-treat population, the complete resection rate was 89.5 % in the A-EMR group and 74.5 % in the C-EMR group (relative risk [RR] 1.20, 95 %CI 1.04 to 1.38; P = 0.01). The en bloc resection rates for the A-EMR and C-EMR groups were 92.4 % vs. 76.4 % (RR 1.21, 95 %CI 1.06 to 1.37; P = 0.005) and R0 resection rates were 77.1 % vs. 64.2 % (RR 1.18, 95 %CI 0.98 to 1.42; P = 0.07), respectively. The median (interquartile range [IQR]) total procedure time was 3.2 (2.6–4.1) minutes in the A-EMR group and 3.0 (2.2–4.6) minutes in the C-EMR group (median difference 0.2 minutes, 95 %CI −0.22 to 0.73; P = 0.25). There was one episode of delayed bleeding and one perforation in the C-EMR group. Conclusions A-EMR was superior to C-EMR for the complete resection of large colorectal polyps. A-EMR can be considered one of the standard methods for the removal of colorectal polyps of 10 mm or more in size.
Freehand endoscopic ultrasound-guided transrectal drainage of diverticulitis-associated abscess with electrocautery-enhanced lumen-apposing metal stent under spinal anesthesia
Authors: Laurent Monino, Philippe Pendeville, Christophe Remue, Tom G. Moreels
Journal: Endoscopy (2022)

Complicated diverticulitis occurs in 12 % of all diverticulitis cases [1]. Radiological drainage is the first-line therapy in cases of large diverticulitis-associated abscess [2]. However, the pelvic location renders the radiological access challenging. Lower endoscopic ultrasound (EUS)-guided drainage, using an electrocautery-enhanced lumen-apposing metal stent (LAMS), is a feasible and safe alternative method for drainage of pelvic collections [3] [4] [5]. We present a case of a diverticulitis-associated abscess successfully treated using EUS-guided LAMS.
Intestinal accumulation of microbiota-produced succinate caused by loss of microRNAs leads to diarrhea in weanling piglets
Authors: Xihong Zhou, Yonghui Liu, Xia Xiong, Jingqing Chen, Wenjie Tang, Liuqin He, Zhigang Zhang, Yulong Yin, Fengna Li
Journal: Gut Microbes (2022)

Diarrheal disease is a common health problem with complex causality. Although diarrhea is accompanied by disturbances in microbial diversity, how gut microbes are involved in the occurrence of diarrhea remains largely unknown. Here, using a pig model of post-weaning stress-induced diarrhea, we aim to elucidate and enrich the mechanistic basis of diarrhea. We found significant alterations in fecal microbiome, their metabolites, and microRNAs levels in piglets with diarrhea. Specifically, loss of ssc-miRNA-425-5p and ssc-miRNA-423-3p, which inhibit the gene expression of fumarate reductase (frd) in Prevotella genus, caused succinate accumulation in piglets, which resulted in diarrhea. Single-cell RNA sequencing indicated impaired epithelial function and increased immune response in the colon of piglet with diarrhea. Notably, the accumulated succinate increased colonic fluid secretion by regulating transepithelial Cl-secretion in the epithelial cells. Meanwhile, succinate promoted colonic inflammatory responses by activating MyD88-dependent TLR4 signaling in the macrophages. Overall, our findings expand the mechanistic basis of diarrhea and suggest that colonic accumulation of microbiota-produced succinate caused by loss of miRNAs leads to diarrhea in weanling piglets.
Fatty liver disease is not associated with increased mortality in the elderly: A prospective cohort study
Authors: Laurens A. van Kleef, Milan J. Sonneveld, Maryam Kavousi, M. Arfan Ikram, Robert A. de Man, Robert J. de Knegt
Journal: Hepatology (2022)

Fatty liver disease (FLD) has been associated with excess mortality. Screening for hepatic steatosis (HS) in patients with metabolic dysfunction is therefore recommended by several guidelines, despite a paucity of evidence on the clinical relevance of FLD in this specific subgroup.We studied participants of an ongoing prospective cohort (the Rotterdam Study). Persons ≥65 years old were enrolled from 2009 to 2014 and were followed through 2018. Steatosis was assessed by ultrasound and liver stiffness (LS) by transient elastography. The association between HS and LS with mortality was assessed using Cox regression analysis adjusted for age, sex, education, smoking, individual components of metabolic syndrome (MetS), heart failure, coronary heart disease, and stroke. We included 4093 elderly participants (74.4 ± 6.6 years old; 42.7% male); 36.8% had ultrasound-based steatosis. During the median follow-up of 6.9 years, 793 participants died (29.6 per 1000 person-years). In the overall population, steatosis was not associated with mortality in multivariable analysis (adjusted HR [aHR], 0.87; 95% CI, 0.73-1.03). Findings were consistent across a range of clinically relevant subgroups, including age categories, sex, MetS, elevated liver enzymes, and cardiac disease. Sensitivity analyses showed similar results for mortality beyond 5 years of follow-up and cancer-related and cerebro-cardiovascular mortality. Furthermore, among participants with steatosis, higher LS (aHR, 1.04 per kPa; 95% CI, 0.95-1.14) was not associated with mortality.Presence of FLD was not associated with mortality in this cohort nor in a range of subgroups. This indicates that screening for FLD and/or fibrosis is unlikely to improve outcomes among the elderly population.
No durable impact of COVID-19 measures on the hospital burden of respiratory syncytial virus (France, 2018–2022)
Authors: Jacques Fourgeaud, Julie Toubiana, Hélène Chappuy, Christophe Delacourt, Florence Moulin, Perrine Parize, Anne Scemla, Hanene Abid, Marianne Leruez-Ville, Pierre Frange
Journal: Journal of Infection (2022)
Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142
Authors: T. André, S. Lonardi, K.Y.M. Wong, H.-J. Lenz, F. Gelsomino, M. Aglietta, M.A. Morse, E. Van Cutsem, R. McDermott, A. Hill, M.B. Sawyer, A. Hendlisz, B. Neyns, S. Abdullaev, A. Memaj, M. Lei, M. Dixon, S. Kopetz, M.J. Overman
Journal: Annals of Oncology (2022)

In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients.Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1).A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation.The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.
Clozapine’s multiple cellular mechanisms: What do we know after more than fifty years? A systematic review and critical assessment of translational mechanisms relevant for innovative strategies in treatment-resistant schizophrenia
Authors: Andrea de Bartolomeis, Licia Vellucci, Annarita Barone, Mirko Manchia, Vincenzo De Luca, Felice Iasevoli, Christoph U. Correll
Journal: Pharmacology & Therapeutics (2022)
Multi-trait and cross-population genome-wide association studies across autoimmune and allergic diseases identify shared and distinct genetic component
Authors: Yuya Shirai, Yoshimitsu Nakanishi, Akari Suzuki, Hachirou Konaka, Rika Nishikawa, Kyuto Sonehara, Shinichi Namba, Hiroaki Tanaka, Tatsuo Masuda, Moto Yaga, Shingo Satoh, Mayuko Izumi, Yumiko Mizuno, Tatsunori Jo, Yuichi Maeda, Takuro Nii, Eri Oguro-Igashira, Takayuki Morisaki, Yoichiro Kamatani, Shingo Nakayamada, Chikako Nishigori, Yoshiya Tanaka, Yoshito Takeda, Kazuhiko Yamamoto, Atsushi Kumanogoh, Yukinori Okada
Journal: Annals of the Rheumatic Diseases (2022)

Autoimmune and allergic diseases are outcomes of the dysregulation of the immune system. Our study aimed to elucidate differences or shared components in genetic backgrounds between autoimmune and allergic diseases.
Object recognition in medical images via anatomy-guided deep learning
Authors: Chao Jin, Jayaram K Udupa, Liming Zhao, Yubing Tong, Dewey Odhner, Gargi Pednekar, Sanghita Nag, Sharon Lewis, Nicholas Poole, Sutirth Mannikeri, Sudarshana Govindasamy, Aarushi Singh, Joe Camaratta, Steve Owens, Drew A Torigian
Journal: Medical Image Analysis (2022)
Ongoing Positive Selection Drives the Evolution of SARS-CoV-2 Genomes
Authors: Yali Hou, Shilei Zhao, Qi Liu, Xiaolong Zhang, Tong Sha, Yankai Su, Wenming Zhao, Yiming Bao, Yongbiao Xue, Hua Chen
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30, 2021, we demonstrate with population genetic evidence that during the course of SARS-CoV-2 pandemic in humans, 1) SARS-CoV-2 genomes are overall conserved under purifying selection, especially for the 14 genes related to viral RNA replication, transcription, and assembly; 2) ongoing positive selection is actively driving the evolution of 6 genes (e.g., S, ORF3a, and N) that play critical roles in molecular processes involving pathogen–host interactions, including viral invasion into and egress from host cells, and viral inhibition and evasion of host immune response, possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution. According to an established haplotype phylogenetic relationship of 138 viral clusters, a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters, of which multiple mutations potentially conferring alterations in viral transmissibility, pathogenicity, and virulence of SARS-CoV-2 are highlighted, warranting attention.
Prevention of sudden death in heart failure with reduced ejection fraction: do we still need an implantable cardioverter‐defibrillator for primary prevention?
Authors: Magdy Abdelhamid, Giuseppe Rosano, Marco Metra, Stamatis Adamopoulos, Michael Böhm, Ovidiu Chioncel, Gerasimos Filippatos, Ewa A. Jankowska, Yury Lopatin, Lars Lund, Davor Milicic, Brenda Moura, Tuvia Ben Gal, Arsen Ristic, Amina Rakisheva, Gianluigi Savarese, Wilfried Mullens, Massimo Piepoli, Antoni Bayes‐Genis, Thomas Thum, Stefan D. Anker, Petar Seferovic, Andrew J.S. Coats
Journal: European Journal of Heart Failure (2022)
PB2043: ERYTHROCYTOSIS IN PATIENTS WITH TIBETAN EGLN1C127S MUTATION: IS IT A POLYMORPHISM IN PATIENTS LIVING AT SEA LEVEL?
Authors: G. Biagetti, A. Benetti, F. Polese, E. Cosi, I. Bertozzi, G. Ceolotto, M. L. Randi
Journal: HemaSphere (2022)

Background: Absolute erythrocytosis is characterized by persistently raised Haemoglobin (Hb) and hematocrit (Ht) levels. Some congenital erythrocytosis (CE) are caused by mutations in a variety of genes, including those involved in the Oxygen-sensing pathway (OSP) (VHL, HIF2a, PHD2) and erythropoietin-receptor (EPO-R) gene. We recently focused our attention on patients with PHD2 mutations, having encountered a number of them affected by erythrocytosis. The EGLN1C127S is considered a polymorphism being very common in Tibetan individuals: in these subjects it facilitates adaptation to high altitude and therefore it is not associated with a phenotype of erythrocytosis. Aims: To study if there is erythrocytosis in PHD2 patients people living at sea altitude like our patients. Methods: We have chosen 12 patients with a PHD2 mutation previously studied with the Sanger method and we re-evaluated them again with NGS panel specific for genes involved in erythrocytosis: JAK2, EGLN1 (PHD2), EPOR, FTL, FTH, ASXL1, HFE, HFE2, TFR2, HAMP, SLC40A1, SLC11A2, VHL, BPMG, EPAS1 (HIF-2α). We then collected their hemoglobin and hematocrit at diagnosis, treatment for erythrocytosis and presence of other relatives with erythrocytotic phenotype. We arbitrarily used phlebotomies to maintain Ht under 50%, or antiplatelet agents to prevent thrombotic complications. Results: The main data of our patients are summarized in the table. The median basal Hb and Ht levels of both patients with Tibetan or other mutations are similar. Two third of patients (66%) needed phlebotomies and 2 patients antiplatelet agents: 6 (85.7%) patients with Tibetan mutation and 4 (80%) of the others with different mutations needed treatment. Three patients had associated mutations: 1 EPO-R A99V, 1 VHL P25L and 1 EPAS1 T766P genes. All of them underwent phlebotomies. Image:Summary/Conclusion: This research shows how most patients with PHD2 mutated erythrocytosis needed a treatment regardless of the mutation. Therefore, we can conclude that EGLN1C127S genotype is associated in our patients with a phenotype of erythrocytosis and necessity of treatment, given the fact that they live at sea level. While the Tibetan mutation facilitates adaptation to chronic reduced oxigen pressure which decreases erythrocytes production in subjects living at high altitude, at the normoxia condition occurring at the sea level the normal process is altered and the erythropoietin gene is activated through not degraded HIF-2 alpha by PHD2. Congenital erythrocytoses are very rare conditions, and those due to PHD2 mutations are only a small part of them. Our study shows an intriguing aspect that needs larger and collaborative researches.
Sequential treatment with bendamustine, obinutuzumab (GA101) and Ibrutinib in chronic lymphocytic leukemia (CLL): final results of the CLL2-BIG trial
Authors: Julia von Tresckow, Paula Cramer, Sandra Robrecht, Petra Langerbeins, Anna-Maria Fink, Othman Al-Sawaf, Moritz Fürstenau, Thomas Illmer, Holger Klaproth, Eugen Tausch, Matthias Ritgen, Kirsten Fischer, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Barbara F. Eichhorst, Michael Hallek
Journal: Leukemia (2022)
Preclinical modeling in leptomeningeal disease: Starting at the foundation to tackle a difficult disease
Authors: Priya Kumthekar, Seema Nagpal
Journal: Neuro-Oncology (2022)

Journal Article Preclinical modeling in leptomeningeal disease: Starting at the foundation to tackle a difficult disease Get access Priya Kumthekar, Priya Kumthekar Department of Neurology at The Feinberg School of Medicine at Northwestern University and The Malnati Brain Tumor Institute at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA Corresponding Author: Priya Kumthekar, MD, Associate Professor of Neurology and Hematology/Oncology, Department of Neurology, The Malnati Brain Tumor Institute at the Robert H. Lurie Comprehensive Cancer Center, 1019 West Monroe Unit 1W, Chicago, IL 60607 (priya.kumthekar@nm.org). https://orcid.org/0000-0001-5923-0677 Search for other works by this author on: Oxford Academic PubMed Google Scholar Seema Nagpal Seema Nagpal Department of Neurology at Stanford University, Department of Neurology, Division of Neuro-oncology, Stanford, California, USA https://orcid.org/0000-0002-0289-2319 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 10, October 2022, Pages 1687–1688, https://doi.org/10.1093/neuonc/noac142 Published: 25 June 2022 Article history Published: 25 June 2022 Corrected and typeset: 30 June 2022
PB1809: CLINICAL TRAJECTORY OF LONG-TERM SURVIVORS OF ACUTE MYELOID LEUKEMIA TREATED WITH INTENSIVE INDUCTION CHEMOTHERAPY
Authors: G. Heering, M. Sasson, D. Dominissini, A. Shimoni, A. Avigdor, A. Nagler, J. Canaani
Journal: HemaSphere (2022)

Background: Notwithstanding the advent of a new era of targeted therapy and innovative molecular breakthroughs seen in acute myeloid leukemia (AML), long-term survival is realized only in a minority of patients. This speaks to the need to thoroughly characterize AML patients achieving long-term survival. Aims: To characterize long-term survivors in terms of baseline clinical, laboratory, cytogenetic, and molecular data and determine whether these parameters differed to a significant degree from a subset of AML patients who died within two years of initial diagnosis. Methods: A single center retrospective analysis of all patients with newly diagnosed AML who were treated with intensive induction chemotherapy from July 1, 2008, through July 31, 2016, and who were alive at least five years from the time of initial diagnosis. Clinical, laboratory, cytogenetic, and molecular data were extracted from the institution’s electronic medical records system. Results: The long-term cohort consisted of 93 patients treated at our institution between the years 2007-2016 with a median follow-up duration of 7.7 years (range 5-13.6 years). Median patient age was 47 years, with 90% presenting with de novo AML. European LeukemiaNet (ELN) 2017 favorable risk patients accounted for 60% of the cohort. All long-term survivors achieved remission following induction chemotherapy. Multivariate analysis showed that compared with 132 patients experiencing death within 2 years of diagnosis, long term survivors were more likely to be of younger age [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.9-0.95; P <.001], have a lower initial WBC count (OR, 0.58; 95% CI, 0.43-0.79; P =0.0004), higher platelet count (OR, 2.19; 95% CI, 1.34-3.57; P =0.0016), undergo an allogeneic stem cell transplantation (OR, 7.95; 95% CI, 3.07-20.59; P <.0001), and harbor favorable risk cytogenetics (OR, 0.03; 95% CI, 0.006-0.23; P=0.0004). Summary/Conclusion: Long-term survival of AML is seen in a distinct demographic and biologic patient subset.
SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection
Authors: Louise C. Rowntree, Thi H.O. Nguyen, Lukasz Kedzierski, Melanie R. Neeland, Jan Petersen, Jeremy Chase Crawford, Lilith F. Allen, E. Bridie Clemens, Brendon Chua, Hayley A. McQuilten, Anastasia A. Minervina, Mikhail V. Pogorelyy, Priyanka Chaurasia, Hyon-Xhi Tan, Adam K. Wheatley, Xiaoxiao Jia, Fatima Amanat, Florian Krammer, E. Kaitlynn Allen, Sabrina Sonda, Katie L. Flanagan, Jaycee Jumarang, Pia S. Pannaraj, Paul V. Licciardi, Stephen J. Kent, Katherine A. Bond, Deborah A. Williamson, Jamie Rossjohn, Paul G. Thomas, Shidan Tosif, Nigel W. Crawford, Carolien E. van de Sandt, Katherine Kedzierska
Journal: Immunity (2022)

As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4